The faculty of two institutions, Weill Medical College and Sloan-Kettering Institute, are requesting funds to support a collaborative training program in basic research in the area of cancer pharmacology. The collaboration consists of an integrated set of training activities for Ph.D. students and postdoctoral fellows. The strength and diversity of the 15 faculty provide opportunities for research in a variety of different areas, such as the development of new cancer therapeutic agents (e.g. through organic synthesis, monoclonal antibody technology, differentiation therapy, and the screening of new compounds), and the analysis of molecular mechanisms by which some drugs cause apoptosis. Research on the control of side effects generated from current treatment modalities [eg. the use of growth factors such as G-CSF to reduce complications associated with bone marrow toxicity] is also a strength. Strategies for overcoming drug resistance are also being developed. Additionally, research concerning the mechanisms by which dioxin and environmental pollutants cause cancer is a part of the training program. The research includes basic mechanistic studies of the molecular actions of drugs used in cancer treatment and cancer prevention, and research leading to more clinical endpoints. The graduate Ph.D. program consists of course work and three lab rotations, followed by an admission to candidacy exam and thesis research. A graduate course in Cancer Pharmacology, initiated ten years ago, is part of this program and represents a commitment of the faculty to the training of students in this area. This training program sponsors a separate seminar series devoted to the area of cancer pharmacology and therapeutics to expose trainees to the research in this area, and students and fellows present their research at the annual two-day Pharmacology Program retreat. Fellows attend a weekly journal club, take courses in cancer pharmacology, and present a formal seminar in the cancer pharmacology seminar series. It is expected that this program will provide students and fellows with a broader understanding of the interrelationships between research on the basic mechanisms of drug action and drug development and clinical issues so that both clinicians and basic scientists will be better prepared to carry out research to prevent or treat cancer. Our request for continued NIH support of a training program in Cancer Pharmacology builds on major commitments of the participating institutions to the enhancement of research in this area. The faculty of this training program are members of the joint WMC/SKI graduate program, with a total of 28 Pharmacology Program faculty. Thus, this faculty represents a cohesive, interactive group of individuals who share a common interest in research and training in the area of cancer pharmacology.